What question did this study set out to answer?

This research aims to evaluate the effectiveness of a therapeutic hepatitis B vaccine and the necessity for additional priming to enhance antibody responses.

March 16, 2026Open Access

Therapeutic hepatitis B vaccine employing DNA prime – MVA boost scheme requires additional priming with recombinant HBsAg to elicit an adequate antibody response

HKHelene Anne KerthHelmholtz Zentrum München MKMartin KächeleHelmholtz Zentrum München NMNikolas MüllerHelmholtz Zentrum München

Key Points

This research aims to evaluate the effectiveness of a therapeutic hepatitis B vaccine and the necessity for additional priming to enhance antibody responses.
Developed a DNA prime-MVA boost immunization regimen for HBV-carrier mice.
Compared the efficacy of sequential versus simultaneous administration of DNA and adjuvanted HBsAg.
Measured CD8+ T-cell responses and antibody titers post-immunization.
DNA prime-MVA boost elicited strong HBV-specific CD8+ T-cell responses.
Sequential administration of HBsAg after DNA priming significantly improved anti-HBs seroconversion rates.
Only the sequential approach supported robust CD8+ T-cell immunity and enhanced neutralizing antibody production.

Abstract

Therapeutic vaccines offer hope for a curative treatment of chronic hepatitis B virus (HBV) infection. We developed a therapeutic hepatitis B vaccine, TherVacB , which employs priming with adjuvanted HBV S (HBsAg) and Core antigens of a single genotype, and a boost with a pan-genotypic Modified Vaccinia Ankara vector (MVA-HBVac) expressing several viral proteins that cover more than 95% of HBV circulating strains. Priming immunization with antigens exactly matching those expressed by the MVA may improve the efficacy of TherVacB . However, recombinant protein antigens need to be produced separately and require complex and costly purification, as well as a Th1-inducing adjuvant, to elicit CD8 + T-cell responses. These limitations may be overcome by DNA vaccines, which enable the direct expression of several antigens in vivo . Here, we investigated the potential of DNA vaccination as an alternative to protein priming to broaden and enhance HBV-specific immunity. Immunization of HBV-carrier mice with a DNA prime-MVA boost regimen elicited robust HBV-specific CD8 + T-cell responses, capable of reducing serum HBeAg levels and eliminating HBV-infected hepatocytes. However, it yielded poor neutralizing anti-HBs titers, resulting in an inefficient reduction of circulating HBsAg. Including adjuvanted HBsAg into DNA priming, either simultaneously or sequentially, significantly enhanced HBsAg-to-anti-HBs seroconversion rates. Still, only the sequential application supported vigorous plasmid-mediated CD8 + T-cell immunity. Interestingly, sequential immunization with DNA, followed by HBsAg and MVA, elicited neutralizing anti-HBs antibodies and enhanced HBV-specific CD8 + T-cell responses, resulting in a more potent antiviral effect compared to the reverse priming regimen. Our study demonstrates that although DNA can successfully prime an effective antiviral CD8 + T-cell response, it requires additional immunization with adjuvanted HBsAg to elicit satisfactory neutralizing antibody titers. In addition, it demonstrates that the sequence of immunizations in multicomponent heterologous-prime boost regimens is crucial and can significantly affect the quantity and quality of induced immune responses.

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